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New treatment option for Desmoplastic Small Round Cell Tumor
Official title Trastuzumab Deruxtecan (DS-8201a) for the Treatment of Recurrent or Refractory Osteosarcoma, Wilms Tumor, and Desmoplastic Small Round Cell Tumor
ClinicalTrials.gov ID: NCT04616560
What this study is testing
What is Trastuzumab Deruxtecan?
Trastuzumab Deruxtecan is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for desmoplastic small round cell tumor.
Also referred to as DS-8201, DS-8201a.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase I/II trial studies the effects of trastuzumab deruxtecan (DS-8201a) in treating patients with osteosarcoma, Wilms tumor (WT) or desmoplastic small round cell tumor (DSRCT) that is newly diagnosed or has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates.
- Phase 2: a mid-size study of how well it works
- This is a blinded study.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 12 to 39
You may be able to join if
- Phase 1 (Part A): Patients must be at least 2 years and less than 12 years of age at the time of study enrollment
- Phase 2: Wilms tumor patients (Part B1): All Wilms tumor patients enrolled must be less than 18 years of age at enrollment
- Until the completion of the Phase 1 dose confirmation, patients must be at least 12 years of age and less than 18 years of age at the time of study...
- Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, Wilms tumor patients at least 2 to...
- Phase 2: DSRCT patients (Part B2): Until the completion of the Phase 1 component, patients enrolling on the Phase 2 component of the study must be...
You likely can't join if
- Pregnant, planning to become pregnant, or breast-feeding women will not be entered on this study. Pregnancy tests must be obtained in girls who are...
- Methods considered as highly effective methods of contraception include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- Oral
- Intravaginal
- Transdermal
See the full eligibility criteria
Who can join
- Phase 1 (Part A): Patients must be at least 2 years and less than 12 years of age at the time of study enrollment
- Phase 2: Wilms tumor patients (Part B1): All Wilms tumor patients enrolled must be less than 18 years of age at enrollment
- Until the completion of the Phase 1 dose confirmation, patients must be at least 12 years of age and less than 18 years of age at the time of study enrollment
- Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, Wilms tumor patients at least 2 to less than 18 years of age will be allowed on the Phase 2 component
- Phase 2: DSRCT patients (Part B2): Until the completion of the Phase 1 component, patients enrolling on the Phase 2 component of the study must be from at least 12 to 39 years of age at the time of study enrollment
- Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, DSRCT patients at least 2 to 39 years of age will be allowed on the Phase 2 component
- Patients must have had histologic verification of Wilms tumor or desmoplastic small round cell tumor at original diagnosis or relapse
- Solid tumors: Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients with clinically inactive brain metastases may be included in the study. Patients with...
- Wilms tumor: WT patients must have either refractory disease or a very high risk relapse, defined as ANY of the following:
- Relapse after initial treatment with 4 or more chemotherapy agents (e.g. Regimens vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide and radiation [M], vincristine, dactinomycin and doxorubicin...
- Relapse with high risk histology (anaplasia, blastemal predominant)
- Multiple relapses
- Desmoplastic small round cell tumor: DSRCT patients with relapsed or refractory disease are eligible
- Patient's current disease state must be one for which they have received at least standard initial therapy, defined as systemic therapy combined with either radiation or surgery for local control of the primary tumor at...
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. Use Karnofsky for patients older than 16 years of age and Lansky for patients 16 years of age and...
- Patients must have recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required...
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator...
- \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
- Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): \>= 7 days after the last dose of agent
- Antibodies: \>= 4 weeks (28 days) must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
- Corticosteroids
- Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7...
- Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
- Stem cell Infusions (with or without total body irradiation [TBI]):
- Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host...
- Autologous stem cell infusion including boost infusion: \>= 30 days
- Cellular therapy: \>= 30 days after the completion the infusion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
- Radiation therapy (XRT)/external beam irradiation including protons: \>= 4 weeks (28 days) including palliative radiation therapy to the chest. \>= 14 days after palliative local XRT to areas other than the chest or for...
- Radiopharmaceutical therapy (e.g., radiolabeled antibody, samarium): \>= 42 days after systemically administered radiopharmaceutical therapy
- Patients must not have received prior HER2 therapies including antibody drug conjugates (e.g. TDM-1 or DS-8201a), HER2 directed cellular therapies, HER2 receptor therapy (e.g. trastuzumab, pertuzumab, margetuximab...
- Patients must be at least 14 days from the date of last surgery
- Peripheral absolute neutrophil count (ANC) \>= 1000/uL, (for patients with solid tumors without known bone marrow involvement)
- Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (for patients with solid tumors without known bone marrow involvement)
- Hemoglobin \>= 8.0 g/dL at baseline (Red Blood Cell transfusion is not allowed within 1 week prior to enrollment) (for patients with solid tumors without known bone marrow involvement)
- For patients less than or equal to 17 years old, "Bedside" Schwartz formula (2009)
- Estimated glomerular filtration rate (GFR) (eGFR) ≥ 70 mL/min/1.73 m\^2 (\> 70mL/min/1.73 m\^2 for patients \> 17 years old)
- For patients older than 17 years of age the Cockroft-Gault equation should be utilized to calculate creatinine clearance ≥ 70 ml/min:
- OR for any age group:
- A 24 hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 (\> 70mL/min for patients ≥ 17 years old) OR
- A directly measured GFR ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per...
- Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age. For patients with documented Gilbert's syndrome (unconjugated hyperbilirubinemia) bilirubin must be \< 3 x ULN for age...
- Aspartate aminotransferase (AST) =\< 3 x ULN
- Serum albumin \>= 2.5 g/dL (patients with solid tumors)
- International normalized ratio (INR)/prothrombin time (PT) =\< 1.5 x ULN. Exception for patients receiving coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have INR/PT within the...
- Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before Step 1 enrollment
- Corrected QT interval (QTc) prolongation to \< 480 ms based on average triplicate 12-lead electrocardiogram (ECG)
- Pulse oximetry \> 93% on room air
- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
- Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) resulting from prior chemotherapy, surgery, and/or radiation must be =\< grade 2, with the exception of decreased tendon...
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment are eligible
- All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
What rules you out
- Pregnant, planning to become pregnant, or breast-feeding women will not be entered on this study. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not...
- Methods considered as highly effective methods of contraception include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- Oral
- Intravaginal
- Transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation:
- Oral
- Injectable
- Implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
- Complete sexual abstinence defined as refraining from heterosexual intercourse. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception
- Non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample...
- Male patients must not freeze or donate sperm starting at enrollment and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to...
- Female patients must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study treatment period, and for at least 7 months after the final study drug administration
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior...
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anti-cancer agents are not eligible
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
- Patients who are receiving chloroquine or hydroxychloroquine within 14 days are not eligible for this trial
- Patients who received a live, attenuated vaccine (messenger ribonucleic acid [mRNA] and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to enrollment are not...
- Note: Participants, if enrolled, should not receive live vaccines during the study and up to 90 days after the last dose of study intervention. It is recommended that patients receive a yearly influenza killed...
- Patients who have received a prior solid organ transplantation are not eligible
- Patients with a medical history of myocardial infarction within 180 days before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) or troponin levels consistent with...
- Additionally, patients with a history of any of the following congenital heart disease are not eligible:
- Single ventricle heart defects (hypoplastic left heart syndrome, unbalanced atrioventricular septal defects, double inlet left ventricle, tricuspid atresia, the presence of superior cavopulmonary anastomosis or Fontan...
- Unpalliated defects with significant hemodynamic alterations or palliated lesions with residual hemodynamic alterations (ductal-dependent or shunt-dependent physiology, large unrestrictive ventricular septal defect...
- Patients who have a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART) are not eligible. (Drainage and...
- Patients who have spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated...
- Patients with a known history of severe hypersensitivity to DS-8201a, any excipient contained in the DS-8201a drug formulation, or HER2-targeted monoclonal antibodies (trastuzumab, pertuzumab, margetuximab) are not...
- Patients who have an uncontrolled infection or non-healing surgical site are not eligible
- Patients with a known history of substance abuse or any other clinically significant medical conditions (i.e. psychological conditions) that may, in the opinion of the investigator, interfere with the patient's...
- Patients who have pulmonary compromise, ex hypoxia, resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the...
- Patients who have a history of (non-infectious) ILD (interstitial lung disease)/pneumonitis that required steroids, has current ILD/pneumonitis, or for whom suspected ILD/pneumonitis cannot be ruled out by imaging at...
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible
- Patients with known hepatitis B or C with detectable viral load are not eligible
- Patients with any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of...
- Patients with an active primary immunodeficiency are not eligible
The study team makes the final eligibility decision.
Where it's taking place
- Birmingham, Alabama, United States
- Los Angeles, California, United States
- Orange, California, United States
- Palo Alto, California, United States
- San Francisco, California, United States
- Aurora, Colorado, United States
- Washington D.C., District of Columbia, United States
- St. Petersburg, Florida, United States
- Atlanta, Georgia, United States
- Chicago, Illinois, United States
- Indianapolis, Indiana, United States
- Baltimore, Maryland, United States
- Boston, Massachusetts, United States
- Ann Arbor, Michigan, United States
- Minneapolis, Minnesota, United States
- Kansas City, Missouri, United States
- St Louis, Missouri, United States
- New York, New York, United States
- Durham, North Carolina, United States
- Cincinnati, Ohio, United States
+ 7 more site(s).
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 12 years to 39 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Birmingham, Alabama, United States; Los Angeles, California, United States; Orange, California, United States; Palo Alto, California, United States; San Francisco, California, United States; Aurora, Colorado, United States and 21 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.